Diagenode

Identification of p21 (CIP1/WAF1) as a direct target gene of HIC1 (hypermethylated in cancer 1).


Dehennaut V, Loison I, Boulay G, Van Rechem C, Leprince D

The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor involved in the regulation of growth control and DNA damage response. We previously demonstrated that p57Kip2; a member of the CIP1/KIP family of CDK (cyclin dependent kinase) inhibitors (CKI); is a direct target gene of HIC1 in quiescent cells. Here we show that ectopic expression of HIC1 in MDA-MB-231 cells or its overexpression in BJ-Tert fibroblasts induces decreased mRNA and protein expression of p21 (CIP1/WAF1) another member of this CKI family that plays essential roles in the p53-mediated DNA damage response. Conversely, knock-down of endogenous HIC1 in BJ-Tert through RNA interference up-regulates p21 in basal conditions and further potentiates this CKI in response to apoptotic etoposide-induced DNA damage. Through promoter luciferase activity and chromatin immunoprecipitation (ChIP), we demonstrate that HIC1 is a direct transcriptional repressor of p21. Thus, our results further demonstrate that HIC1 is a key player in the regulation of the DNA damage response.

Tags
Bioruptor
Chromatin Shearing
ChIP-qPCR

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Published
November, 2012

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